Genetics&the Child with Autism

Description

Autism spectrum disorder affects 1 in 110 children in the U.S. This lifelong developmental disorder affects development and learning, and significantly influences how children understand and relate to the world.

Early identification of children with autism is crucial in order to provide the individualized treatment they need to provide the best outcome in life. Families and caregivers of autistic children also require attention to help build relationships and relieve stress caused by this medical condition.

A strong focus on utilizing applied behavior analysis (ABA) to teach autistic children basic and complex skills is effective in modifying the consequences of behavior. As such, children learn appropriate behavior and decrease the use of inappropriate or interfering behavior. Opportunities for success are built into the program. Adjustments are made as children progress, helping them to function with increased independence.

A multidisciplinary approach with an expert team of specialists helps ensure the most appropriate care is provided to a child who is suffering from autism.

Every child deserves the opportunity to learn, laugh and play to become healthy, happy and productive adults.

About the Speaker

Thomas W. Frazier II, PhD, is the interim director of Cleveland Clinic Children’s Hospital Center for Autism and a staff member with Center for Behavioral Health. He also is the research director of the Center for Autism, and jointly appointed in the Genomic Medicine Institute and in the Lerner College of Medicine.

Dr. Frazier completed his fellowship in neuropsychology at Cleveland Clinic’s Department of Psychiatry and Psychology, Section of Neuropsychology, and an internship in clinical psychology at the United States Department of Veterans Affairs, VA Ann Arbor Healthcare System, Ann Arbor, Mich. He completed his master’s and doctoral degrees in clinical psychology at Case Western Reserve University.

Dr. Frazier’s primary clinical interests include the assessment and behavioral treatment of individuals with autism spectrum disorders. Dr. Frazier also specializes in the assessment and differentiation of pediatric bipolar disorder, attention deficit hyperactivity disorder (ADHD) and other disruptive behavior disorders in his clinical practice.

Timothy Moss, MD, PhD is an assistant staff member with Cleveland Clinic Genomic Medicine Institute with a joint appointment in the Lerner Research Institute.

Dr. Moss completed his residency in clinical genetics at Baylor College of Medicine Affiliated Hospitals, in Houston, TX. He received his medical degree and doctoral degree from the University of Iowa College of Medicine, Iowa City, IA.

Let’s Chat About Genetics and the Child with Autism

Cleveland_Clinic_Host: Dr. Moss, would you start us off with a little information about autism spectrum disorders, or ASD?

Timothy_Moss,_MD,_PhD: Public awareness of autism spectrum disorders has increased secondary to many reports in the media. This has coincided with an increase in the diagnosis rate for reasons that are still under debate, but primarily involves increased screening and recognition. There is a wide range in how much the disorders affect people in their daily life, and no two people are the same. Concern for autism spectrum disorders can be brought up by many people, but diagnosis is done by professionals such as those found at Cleveland Clinic Children’s Hospital Center for Autism. While autism can run in families, not all autism can currently be shown to have a genetic basis. However, the standard of care for those diagnosed with autism includes a genetic and metabolic evaluation to look for treatable and inherited forms of autism, which can account for anywhere from 10 to 20 percent of diagnosed autism spectrum disorders.

Autism Spectrum Diagnosis

hold on: I’ve recently seen a documentary on autism. When they described the characteristics, I see a lot of the signs in my three-year-old son. Yet, there are some characteristics that were not present. How is autism diagnosed and are there different degrees? Are there certain characteristics that a child must have in order to be diagnosed as autistic?

Thomas_W._Frazier_II,_PhD: Not all characteristics need to be present for a child to have autism. In fact, the spectrum is very wide and no two children with autism look the same. Specific characteristics will vary. Broadly, children with autism all have some form of social communication problem coupled with some form of repetitive or preservative behavior. Preservative behavior refers to getting stuck on a topic, interest, idea, motor movement, routine, etc. Social communication problems vary, but in all cases they involve some difficulty with taking the perspective of others and using that information to guide their own behavior.

Peaches7: I have a great-nephew who has been diagnosed with autism. I am very concerned that my granddaughter is struggling with Asperger syndrome, and it has been ignored for many years. She is now 21 years old, and her struggles are becoming much more apparent. Even though my daughter is very aware that her cousin's son has an illness that is connected, she is still in denial. Therefore, nothing is done to help my granddaughter. Is there a way I can share the correlation between these two illnesses to my daughter to help her see how serious this is and that there is help? I don't know what to do to obtain the help my granddaughter needs.

Thomas_W._Frazier_II,_PhD: Asperger syndrome and autism are connected as they are both part of the autism spectrum and will both fall under the new DSM-5 criteria for autism spectrum disorder. I would focus though on your granddaughter’s problems and trying to get her help for those problems. Sometimes people become defensive when talking about diagnoses, but most people can recognize a problem. That will help them get to a professional, such as a clinical psychologist, who can evaluate the problem and provide recommendations for treatment.

Benefits of Early Diagnosis

buster54: I am a retired school bus driver of 32 years, and I mainly drove special needs children. My question is a family at church has a four-year-old boy. His motor skills are delayed along with his speech. He is doing thing like running in circles until you tell him to stop, and jerks one hand over and over. He is a very happy child with a great imagination, but his mother is the only one who can understand him when he talks. He is smart in many ways, but these other things are worrying us. His mom is very protective, and this is their only child. If autism is diagnosed early, can it be helped? How do you talk to mother and father about such concerns?

Thomas_W._Frazier_II,_PhD: This child is displaying many of the characteristics of children with autism, and should receive an evaluation. I would talk with them about getting an evaluation, so that they can understand better what they can do to help their child develop socially and be understood by others. It is a tricky conversation, but ultimately being honest and open is important. Even if they don’t listen to you, they may hear it better from the next person who tells them the same thing.

Genetic Basis of Autism

trudy993: What are the genetic causes of autism?

Timothy_Moss,_MD,_PhD: There are too many genetic causes of autism to list. Currently, the rate of genetic causes of autism is reported to be 10 to 20 percent, depending on what studies are included. These causes range from misspelling in genes (the instructions of the human body) to deletions or duplications of large amounts of genetic material. Most forms of autism do not have a cure, but there are some very rare inborn errors of metabolism caused by genetic defects where diet or medicine can reduce the severity.

One must also be take into consideration that there are people with autism only, and there are people with autism plus other medical problems that are included as part of a genetic syndrome. These other problems, such as birth defects, heart defects or dysmorphic features often suggest that there is a genetic syndrome as the underlying cause of the autism. Currently, a baseline genetic and metabolic evaluation is the standard of care for most people diagnosed with autism.

hannahj8: Are the inherited forms of autism still part of the spectrum, or are they basically the discovery of an underlying problem with autism- like symptoms?

Timothy_Moss,_MD,_PhD: We can see genetically inherited forms of autism that encompass all parts of the spectrum. Autism can be part of a syndrome with more medical problems, or it can be the only medical problem and still be caused by a single genetic defect.

meue01: How would we know if the autism is inherited or not? This is especially important to me since years ago they only diagnosed more severe cases and not higher-functioning individuals.

Thomas_W._Frazier_II,_PhD: The first studies to identify genetic causes of autism were based on twin studies. These studies have been well replicated and include higher- functioning individuals now. So, it is not likely that the expanding spectrum will greatly influence these findings. Thus, it seems that even when higher-functioning cases are considered, autism continues to show a pattern of strong genetic influences.

Genetic and Metabolic Study in Autism Patients

cord: We participated in a few genetic studies, but I’m not sure about a metabolic study or evaluation. Should my children have a metabolic evaluation to see if there are any underlying treatable disorders in addition to autism?

Timothy_Moss,_MD,_PhD: Usually the healthcare professionals that ordered the genetic studies include the metabolic studies as part of the initial work-up for autism. Without knowing what specific studies are done, it is hard to say if more tests need to be ordered. While there are some very rare cases of inborn errors of metabolism causing autism that have a partial treatment, those are often the disorders and tests we look for first because they are treatable. The other thing to take into consideration is that medical knowledge and technology is changing very rapidly in genetics, so it is never a bad idea to touch base every few years with the medical provider who did the initial testing to see if something more is indicated.

cord: Is there a Cleveland Clinic website that will give me more information on what this type of evaluation entails? It is better for me to know what I am asking s physician to do than have them guess what I mean.

Timothy_Moss,_MD,_PhD: My recommendation would be to have the affected individual evaluated at a center that specializes in autism or at a genetics clinic. They are the best equipped doctors to evaluate what testing has been done and what more is needed. In terms of a specific website that has them listed, there are several medical journal articles that discuss different versions of the standard of care in metabolic evaluation, but your best bet is to go and see someone at a genetics clinic or autism center.

dcat: If we already have an autism diagnosis and are not planning to have other children, what are the benefits of doing genetic testing now? Specifically, what are other medical problems that you would be looking for?

Timothy_Moss,_MD,_PhD: It all depends on what other medical problems are occurring in the affected person. If it is isolated autism, there are some rare causes of autism that have medication or dietary changes that can help mitigate symptoms. Alternately, if it is a syndromic version there can be some occult problems such as adult onset neurologic problems, increased tumor risk and occult congenital anomalies. Going to a genetic doctor for counseling does not mean that testing will be done, but that is the best way to have the discussion like this, so the information can be specific to that patient.

Sibling Genetic Testing

shadow12: Is there any data on typical siblings as far as potential to have offspring with autism, and any genetic testing they should have? How often do you recommend genetic testing for children with autism? If you had a child tested when they were two years old and again in his or her teens with all the results being fine, is there a need for further testing at some point?

Timothy_Moss,_MD,_PhD: Currently, the best and most recent sibling study suggested a rate of 15 to 20 percent. It is even higher if the child is male or if they are more than two children in the family with a diagnosis. Currently, anyone diagnosed with autism should have a preliminary genetic and metabolic evaluation, and this is even more indicated if it runs in the family. In terms of follow-up or repeat testing, it depends on when the initial evaluation was conducted. The molecular causes of autism have really only started to be discovered in the last 10 to 15 years, with the majority of them in the last few years. As such, we currently would recommend touching base ever few years with the provider who did the initial testing. For someone who has had recent testing and is in their teens to 20s, this probably lengthens out to every five to 10 years. However, every patient and person is unique—so the best answer is to follow what the doctor who did the repeat testing said to do about follow up.

MartM: My son has moderate-to-severe autism. Should his brothers be tested for genetic markers before they decide to have children?

Timothy_Moss,_MD,_PhD: To answer that question, one must first know if your son has a known molecular or genetic reason for his autism. If the brothers do not have autism, without knowing what exact genetic change to look for, it would be hard to give any sort of risk assessment.

Cole-Hughes Syndrome and Autism

tmsports: I am a school nurse and one of my students has been diagnosed with autism associated with Cole-Hughes syndrome. Are you finding correlations in others with Cole-Hughes syndrome? She has a complex diagnosis including type 2 diabetes.

Timothy_Moss,_MD,_PhD: Cole-Hughes syndrome has multiple reports of autism spectrum associated with that diagnosis. It can also be associated with other problems such as a large head (macrocephaly) and characteristic facial features. It can be associated with obesity as well, which could predispose her to diabetes. Alternately, diabetes is very common in the population and sometimes individuals with uncommon syndromes also have unrelated common medical problems.

Autism and Alzheimer Disease

cubfan01: What are you learning about a possible connection between Autism and Alzheimer disease? My son has autism and my father- in-law has Alzheimer disease.

Thomas_W._Frazier_II,_PhD: We know very little about this connection, but there may be genes that overlap such as PINK1. It will take additional family studies to look at whether there is a connection. Given the frequency of Alzheimer disease and autism, it is possible that there is no real link.

cubfan01:Is there anything we can do to help with this research into a link between autism and Alzheimer disease since our family is affected by both?

Thomas_W._Frazier_II,_PhD: Please contact me about this possibility as we are looking at studies that are a first step toward understanding this issue. The phone number for Cleveland Clinic Children’s Hospital Center for Autism is 216.448.6440.

Birth Complications and Autism

Thomas_W._Frazier_II,_PhD: Birth complications have been linked to autism, but the increase in risk is small. What this means is that in an individual circumstance it is not a 1:1 correspondence between the complication and autism, but it may contribute to risk in an otherwise genetically at-risk individual.

Trigger Events

hannahj8: Some of the books I've read have described autism as a genetic predilection that starts after a triggering event sometime in early childhood. Is this model still current? Has research identified what types of events are ‘triggering’? Will genetic research be able to isolate these events or do they need to be found from a behavioral or patient history perspective?

Thomas_W._Frazier_II,_PhD: Autism is a highly heritable disorder with likely many genes (over 500 are involved). However, it may only be one or a few genes affected in a specific individual. The model of a trigger event is less prevalent now as we have been able to identify genetic causes that probably operate throughout development including in utero. There are a small proportion of children with autism who show very unusual patterns of development such as regression. These individuals may have some events which make their autism symptoms more apparent or obvious to the parent.

Behavioral Issues of Autism

meue01: My son was diagnosed with autism spectrum disorder (ASD) when he was two years old through the school district. He received applied behavior analysis therapy at home and in school, but it was minimal. He is now 10 years old and in the fourth grade. The school dropped his services in second grade as they could find nothing more for him to work on, and we, as parents, agreed. He only has behavioral issues at home and no where else. Could this be a typical child misbehaving or should we be treating it as a symptom of ASD.

Thomas_W._Frazier_II,_PhD: I think the question is better framed as what are the behavior problems, what is driving these problems, are they persistent, and do they require intervention? If the problems are persistent then it really doesn't matter if they are part of development or part of ASD, they need to be addressed. I would look to a competent provider to help with treating these. This may involve parent coaching with a psychologist or behavioral expert (preferably BCBA™ [board-certified behavior analysis] provider, who can be found at www.bacb.com). The point is to identify the cause of the behavior problem and then develop a treatment that is appropriate.

cord: It’s hard for my child to communicate pain. Now that she's starting to a little bit, how do I take that into consideration with her self-injurious behavior (SIB), as well as aggressive and repetitive behaviors? I need suggestions for talking to physicians about ruling out actual stomach pain or ear pain before moving forward with behavior plan.

Thomas_W._Frazier_II,_PhD: Ruling out physical problems when a child is showing SIB/aggressive behavior is key, but often difficult. I recommend getting a full functional behavioral assessment by a qualified behavior therapy provider to determine the function of any challenging behavior in a minimally verbal person with autism. These providers can help to identify the function or motivation for the behavior. If the motivation appears to be physical pain, they can also identify that possibility. Once that assessment is completed, it may be easier to speak with physician providers about the presence of pain or other medical problems. In terms of your child's communication of this problem, it is important to continue to give them a chance to tell you what is wrong, possibly even using visual cues to provide information about whether they feel pain.

Behavioral Therapy

CLStar: Where does one get behavior therapy?

Thomas_W._Frazier_II,_PhD: There are many ways to try to access behavior therapy services. Some schools are becoming savvier in delivering behavior therapy-based educational services. There are providers who specialize in the delivery of behavior therapy (go to www.bacb.com to locate board-certified behavior analyst providers). Treatment centers such as Cleveland Clinic Children’s Hospital Center for Autism also offer services depending on the child's needs.

Programs for Autistic Adults

CLStar: I know there are many opportunities for the autistic child nowadays. However, when my son was young there were no such opportunities. It was hard to even get a diagnosis. Today he is 49 years old. He volunteers at the Kent State University library where he has shelved book for the past almost 28 years. Is there anything out there now for the autistic adult? In the age of computers, I hear rumors of libraries going away. If so, he will spend his day in his room and that is no life for anybody. Autistic adults need programs and/or jobs.

Thomas_W._Frazier_II,_PhD: There is increasing recognition of the need for adult services. At Cleveland Clinic’s Lerner School we have begun to ensure that children transition from school services to supported employment for those who have reached the age of 22 years old. The bad news is that the creation of adult services and supported employment is likely to be slow over the next decade. The good news is recognition is increasing and with it funding will follow.

CLStar: What about the autistic adult that never got the help that is available to today's child? Is it too late for them?

Thomas_W._Frazier_II,_PhD: It is definitely not too late. In older children and adults, treatment can be effective in building skills, increasing social behavior and improving overall functioning. Behavior therapy can be just as effective with adults as children with autism.

Autism Genetic Research

nystrom: Is there ongoing research that connects a genetic component (like a missing gene or a gene defect) to autism?

Timothy_Moss,_MD,_PhD: Research into autism is a very hot topic at the moment, and has good research funding. This means there is a lot of research going on, focusing on looking for changes, or mutations, in single genes that can cause or increase the risk of autism. It also includes environmental effects and epigenetic causes or risks (i.e., changes in gene expression and not in gene sequence). Similarly, there are ongoing studies looking at how to make the most of skills that people with autism have. Currently, the standard of care for autism includes looking for known genetic defects or inborn errors of metabolism that cause autism. Finding one of those changes in an individual can help families and individuals know if there are other medical problems that they should worry about besides autism. This revelation can also help in determining whether another family member is at risk for autism. When looking for genetic causes of autism, we do try to focus on those causes that have specific medical treatments that help reduce the severity of problems—although at the moment those causes are few and far between. However, literally every month there is new research being published that helps in diagnosis and treatment.

keareb:How will the pending Supreme Court case regarding genetic patents impact genetic research, testing and potential treatment of autistic syndrome disorder children? In your opinion, what would be the preferred outcome of the case?

Timothy_Moss,_MD,_PhD: This is a very controversial subject in genetics that we talk about at our national meetings each year. As both a researcher and clinician I have had difficulty in working or making diagnoses with genes for which a company holds a patent. On the other hand, I can see why patents provide incentives for some companies, too, for the time and resources to make a test clinically available. Without bias I can say that those companies with patents that are the only provider of a gene test often charge more than those tests than are offered by multiple companies. However, those same patent-holders often have programs in place to help very low income patients.

My personal opinion is that gene patents inhibit research and low-cost testing, not just for autism but for most genetic disorders. A middle-of-the-road solution with a short-term patent may be the best of both worlds, but the current case before the United States Supreme Court is focused partly on if one can even patent a gene as it is a product of nature—like sunlight. The argument of the company is that the technology to remove the gene from the natural environment and do something with it is what is being patented. I personally do not feel that to be the case, but there are good reasons for both sides of the argument.

shadow12: Which country to date is conducting the most research on autism and genetics?

Thomas_W._Frazier_II,_PhD: As with most scientific research, the U.S. is by far the leader in investigating the genetics of autism.

alibh52: What do genetic studies reveal about autism? Can the genetic anomaly be located in a relative to the child? More importantly, can the anomaly be predicted in a sibling's children in the future?

Timothy_Moss,_MD,_PhD: If the exact genetic or molecular cause of the autism is known, then one could look for the same genetic in an at-risk relative. Who is at risk depends on what type of genetic change occurred, and is best evaluated by a genetics counselor or physician. Once the molecular cause is known, we can provide more specific numbers on the chance of it happening again. There is also preimplantation genetic testing available for some genetic disorders if in vitro fertilization is used, or prenatal testing via chorionic villus sampling or amniocentesis can be used to identify some affected pregnancies. For current siblings, at-risk individuals like a sibling can be tested depending on what the exact molecular change was and the age of the sibling.

shadow12: How fast is research progressing, and do you envision treatments on the horizon?

Thomas_W._Frazier_II,_PhD: Research is a slow process and it will likely be a decade or more before personalized genetic-based treatments are available for the majority of children with autism. However, there are advances being made everyday. As we learn more about the genetic causes and underlying biology, it is becoming easier to identify promising treatment approaches. The advent of stem cell approaches that allow researchers to study the brain cells of individuals with autism and investigate treatments of abnormalities in brain structure or function without having to give patients medicine is an important step forward. This step will speed discover of medicines that can help individuals with autism.

PhilR:Any new studies tying autism to autoimmune problems?

Timothy_Moss,_MD,_PhD: It all depends on whether there is a known syndromic component to the autism. Some genetic syndromes that have other medical problems in addition to autism can have related autoimmune problems. However, both autism and autoimmune issues are by themselves incompletely understood at the genetic level and research is active in these fields.

Environmental Factors and Autism

Alc:With genetics explaining only part of the picture, what else is being investigated? What environmental causes are being looked at in the research, and what is your opinion on their likely role?

Thomas_W._Frazier_II,_PhD: We suspect based on heritability studies that genetics contributes to a substantial proportion of autism spectrum disorder with some estimates as high as greater than 90 percent of the cause of autism due to genes. There are studies looking for environmental risk factors. To date, a few have been replicated and these further suggest a role for genes. For example, advanced paternal age has been replicated as a risk factor and this factor is likely due to the increased mutation load that older fathers transmit to offspring. Another factor identified is the use of folate during pregnancy. Folate is important for the integrity of our genes and gene expression. It is very challenging to investigate environmental risk factors because large samples are needed. By identifying genes contributing to autism, it may assist in the search for environmental risk factors by pointing toward ways in which the environment might alter biology.

Timothy_Moss,_MD,_PhD: There are a number of chemicals or teratogens that are known to cause birth defects during pregnancy. For example, even alcohol, which can cause fetal alcohol syndrome producing significant medical and behavioral problems. In terms of causing isolated autism that would be a very, very rare and hard connection to make. However, there are environmental-genetic interactions that are termed epigenetics that are currently being investigated as a reason for autism. The research in this area is very interesting and active.

For More Information

On Cleveland Clinic

Our team at Cleveland Clinic Children’s Hospital Center for Autism believes that all children deserve the opportunity to laugh and play and to become healthy, happy and productive adults. We provide specially designed diagnostic, treatment, and education services to reach those goals. We also offer consultations and conduct training and research to improve the lives of children with autism and their families.

Specialists at the Center for Autism, including psychologists, speech-language pathologists, behavior therapists, teachers, intervention specialists and consulting physicians, develop individual programs for each child, depending on his or her need. They provide diagnostic and follow-up evaluation, speech, language, and communication services, behavioral and educational consultation, functional behavior assessment, behavior therapy and consultation and intensive behavioral intervention. All programs rely on current evidence-based research, with a strong focus on applied behavior analysis (ABA).

The Center also houses the Lerner School. This chartered, non-public day school, certified by the state of Ohio, serves students from diagnosis to the age of 22 years old.

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